What are the treatment options for genital herpes?

Treatment of Genital Herpes

For genital herpes, use oral antiviral therapy with acyclovir, valacyclovir, or famciclovir, with treatment approach determined by whether this is a first episode, recurrent outbreak, or need for suppression—valacyclovir offers the most convenient dosing with once-daily options for suppression and 3-day regimens for recurrences. 1, 2

First Clinical Episode

For patients presenting with their first genital herpes outbreak, initiate treatment immediately:

• Acyclovir 400 mg orally 5 times daily for 7-10 days until clinical resolution 1
• Alternative: Acyclovir 200 mg orally 5 times daily for 7-10 days 1
• For herpes proctitis specifically, use acyclovir 400 mg orally 5 times daily for 10 days 1

The CDC guidelines emphasize treating until clinical resolution is achieved, which may extend beyond the standard duration in some cases. 3

Recurrent Episodes: Episodic Therapy

When patients experience recurrent outbreaks, they should self-initiate treatment at the first sign of prodromal symptoms or lesions for maximum effectiveness:

Preferred regimen:

• Valacyclovir 500 mg orally twice daily for 5 days 1, 2

Alternative regimens (all equally effective):

• Acyclovir 400 mg orally three times daily for 5 days 1, 2
• Acyclovir 800 mg orally twice daily for 5 days 1, 2
• Acyclovir 200 mg orally five times daily for 5 days 1, 2
• Famciclovir 125 mg orally twice daily for 5 days 1, 2

Valacyclovir also offers a 3-day regimen option (500 mg twice daily for 3 days), which is the only FDA-approved short-course therapy, though the 5-day regimen remains standard in CDC guidelines. 4, 5

Episodic therapy works best when started during the prodrome or within 1 day of lesion onset. 2 The median time to lesion healing with valacyclovir 500 mg twice daily is 4 days versus 6 days with placebo. 4

Suppressive Therapy

Offer daily suppressive therapy to all patients with symptomatic HSV-2 infection, particularly those with ≥6 recurrences per year. 3, 1, 2

Preferred regimens:

• Valacyclovir 1,000 mg orally once daily 1, 2
• Valacyclovir 500 mg orally once daily 1, 2

Alternative regimens:

• Acyclovir 400 mg orally twice daily 1, 2
• Famciclovir 250 mg orally twice daily 1, 2

Key Benefits of Suppressive Therapy:

• Reduces recurrence frequency by ≥75% in patients with frequent episodes 1, 2
• Reduces asymptomatic viral shedding 2
• Decreases transmission risk to uninfected sexual partners 3, 4
• Safe for extended use (up to 6 years with acyclovir, 1 year documented with valacyclovir) 2

Dosing Strategy by Recurrence Frequency:

• Patients with <10 recurrences per year: Valacyclovir 500 mg once daily is sufficient 6
• Patients with ≥10 recurrences per year: Valacyclovir 1,000 mg once daily, valacyclovir 250 mg twice daily, or acyclovir 400 mg twice daily 6

After 1 year of continuous suppressive therapy, consider discontinuation to reassess the patient's recurrence rate. 2

Severe Disease Requiring Hospitalization

For severe genital herpes requiring hospitalization (disseminated infection, CNS involvement, or inability to take oral medications):

• Acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days or until clinical resolution 1

Special Populations and Situations

HSV-1 vs HSV-2

• The same medication dosages and frequencies are recommended for genital HSV-1 infection, though genital HSV-1 has been less comprehensively studied than HSV-2. 3

Immunocompromised Patients

• Antiviral resistance is rare in immunocompetent patients but more common in immunocompromised individuals 1
• Higher doses may be required: acyclovir 400 mg orally 3-5 times daily until clinical resolution 7
• For severe cases: IV acyclovir 5-10 mg/kg every 8 hours 7
• If lesions do not resolve within 7-10 days of therapy, suspect acyclovir resistance and consider foscarnet 40 mg/kg IV every 8 hours 2, 7

Asymptomatic HSV-2 Infection

• Approximately 20% of HSV-2 seropositive persons do not report genital symptoms 3
• Suppressive therapy can be offered to reduce asymptomatic viral shedding and transmission risk, though this population may not recognize their need for treatment 3

Prevention of Transmission

• Suppressive therapy reduces transmission to uninfected partners in heterosexual couples through suppression of viral shedding 3, 4
• This mechanism applies to all populations (MSM, women who have sex with women, transgender persons), though formal studies were conducted in heterosexual couples 3
• Important exception: Suppressive therapy is NOT effective for decreasing transmission risk in persons with HIV/HSV-2 coinfection 3

Important Clinical Pitfalls

What NOT to Use:

• Topical acyclovir is substantially less effective than oral therapy and should NOT be used 1, 2, 7
• Avoid valacyclovir 8 grams per day in immunocompromised patients due to risk of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura 2

Patient Counseling Essentials:

• Genital herpes is a recurrent, incurable viral disease 2
• Antiviral medications control symptoms but do not eradicate the virus or prevent all recurrences 1, 2
• Asymptomatic viral shedding can occur, potentially leading to transmission even without visible lesions 1, 2
• Abstain from sexual activity when lesions or prodromal symptoms are present 1, 2
• Use condoms during all sexual exposures with new or uninfected partners 1, 2
• Inform sexual partners about having genital herpes 2

Serologic Testing Considerations:

• Do NOT screen asymptomatic persons with low pretest probability 3
• Do NOT screen pregnant women routinely 3
• DO test persons with genital symptoms consistent with herpes (classic or atypical) 3
• DO test persons told they have genital herpes without virologic confirmation 3
• DO consider testing persons at increased epidemiologic risk (e.g., partners of HSV-2 positive individuals) 3

Practical Dosing Advantages

Valacyclovir offers significant adherence advantages due to less frequent dosing compared to acyclovir, which requires 5 times daily dosing for first episodes. 3, 8 The once-daily suppressive option and 3-day episodic treatment regimen make valacyclovir particularly practical for real-world use. 8, 5